1. Field of the Invention
The present invention relates to a composition having anti-oxidative activity that is derived from natural extracts of animals and plants, and more particularly to an antioxidant composition that can exhibit anti-oxidative activity in the living body against active oxygen species which are produced in the body. The present invention provides a novel antioxidant composition that enables the preparation of food products and food product ingredients that provide protection against a wide range of lifestyle diseases, more specifically, protection against diabetes-related diseases in diabetic patients who have a markedly high level of active oxygen, by eliminating oxidative stress caused by active oxygen produced within the body.
2. Description of Related Art
In recent years in Japan the increasing number of various geriatric diseases associated with an aging population and the increased human and economic burden of medical care thereof have become extremely serious problems. The aging of organisms and the onset of disease are, in a sense, inextricably related, and therefore it is unavoidable that as the population ages, the number of people with diseases will also increase. Thus, it is important to delay the progression of aging in humans as much as possible to suppress the onset of disease.
The primary cause of aging in human beings is the fact that the cells constituting the body are limited in the number of times they can divide and propagate to regenerate tissue, and the number of cellular divisions reaches its limit and tissue regeneration capability decreases because cells are subjected to various kinds of damage. Aging progresses due to factors that damage cells, for example, exposure to ultraviolet light and radiation, chemicals, etc., and to active oxygen that is produced within the bodies of living organisms. More specifically, active oxygen is a substance that is naturally produced by organisms that utilize oxygen to perform energy metabolism, and in that sense, it can be said that the aging we undergo occurs naturally. Therefore, the suppression of the harmful effects of active oxygen that is produced within the body plays an important role as a primary countermeasure to delay aging and suppress the onset of age-related diseases.
In the past various antioxidants have appeared on the market, but almost all were prepared from a single constituent or single starting material. However, there are many different active oxygen species produced in the body, and concrete examples include superoxide (O2−) produced from oxygen gas incorporated into the body. This O2− is converted to hydrogen peroxide (H2O2) by an enzyme called superoxide dismutase (SOD), and the H2O2 goes on to generate a hydroxyl radical (OH•) by transition metal catalysis. In addition to H2O2, white blood cells produce active oxygen to destroy bacteria that invade the body, and these forms of active oxygen include the hypochlorite radical, nitric oxide radical, etc.
On the one hand, various species of antioxidants are used to remove these types of active oxygen, but sufficient investigations have not been performed to determine whether these antioxidants are effective against all active oxygen species or only a limited number of species thereof. The inventors investigated the effects of antioxidants on the oxidative degradation of protein by various active oxygen species, and these investigations revealed that different antioxidants are effective against different active oxygen species, and there are very few antioxidants that are effective against all active oxygen species in the body. In other words, substances that have potent antioxidative action include the following: against the hypochlorite radical (ClO•), the peptides anserine and carnosine, reduced glutathione (GSH), and sulfur-containing amino acids or analogs thereof that are present in the bodies of various species of animals; against the peroxynitrite radical (ONOO•), vitamin C (L-ascorbic acid, V.C.); and against the hydroxyl radical (OH•), vitamin E (α-tocopherol, V.E.). It has already been confirmed that combinations and compositions of antioxidants wherein antioxidants are used together rather than independently are effective in completely eliminating the damage caused by active oxygen produced in the body (see Japanese Patent Application No. 2003-025210).
In the past various antioxidants have been tested for the prevention of various types of diseases, and lifestyle diseases in particular. For example, these include polyphenols such as V.C., V.E., β-carotene, catechins, etc. However, when we look at the prevention of diseases, e.g., the prevention of diseases such as cancer, etc., by these antioxidants, few findings show that they are effective. Conversely, most results show that they have no clinical efficacy (see J. Kaikkonen, et al. Free Radicals Research, Vol. 33, p. 329-340, 2000), and antioxidants have not provided the effect of preventing diseases and aging as much as had been expected. Possible causes include the following: first, there are many active oxygen species produced in the body, and it is almost impossible to eliminate all of their damaging effects with a single antioxidant; furthermore, with the exception of V.C., most of the other antioxidants derived from plants have a structural backbone such as a phenol group, etc., that exhibits the property of lipid solubility, and polyphenols are so poorly absorbed by the human gastrointestinal tract that the amount absorbed into the body is no more than 1/1000 of the amount ingested orally, etc. Therefore, most of these antioxidants have not sufficiently displayed efficacy in the body even when they have demonstrated extremely potent antioxidant activity in vitro.
To overcome these deficiencies, it is important to have an antioxidant composition that can counteract the wide range of active oxygen species and to select materials that can sufficiently counteract the OH• produced in the process of energy metabolism. As noted above, the peptides anserine and carnosine, reduced glutathione (GSH), and sulfur-containing amino acids obtained from animal materials have strong antioxidant activity against ClO•; V.C., which is a water-soluble vitamin, has strong antioxidant activity against ONOO•; and V.E., which is a fat-soluble vitamin, has strong antioxidant activity against OH•. However, the strong antioxidant activity of V.E. against OH• is one that inhibits proteolysis, and when we compare it with other antioxidants derived from plants, this activity is approximately 1/5000 that of the carotenoid astaxanthin, 1/2000 to 1/1000 that of the polyphenol catechins and quercetin, and 1/1000 to 1/500 that of caffeic acid derivatives (Table 1). Therefore, even though V.E. is absorbed well by the gastrointestinal tract and it is distributed throughout the whole body, a large amount must be ingested to scavenge OH•. However, there are problems with V.E. because the maximum daily dose to be taken by adults is 300 mg, it is harmful if taken in excess, and because it is an oil, it suffers a loss of antioxidant activity during storage and food processing becomes difficult.